Search Results (119)

Perfluorononanoic acid (PFNA) is a ubiquitous persistent environmental pollutant, and several studies have found significant links between atopic dermatitis (AD) and prenatal exposure to PFNA. However, the relationship between PFNA and AD remains unclear. In this study, 2,4-dinitrochlorobenzene (DNCB)-treated female BALB/c mice were used as AD models to investigate the effects of PFNA and its potential mechanisms. These mice were topically applied with 5 mg/kg PFNA per day for 15 days. The results demonstrated that PFNA significantly increased AD lesion severity and clinical symptoms, including dermatitis score, ear thickness, and epidermal thickness. In addition, PFNA also increased the serum IgE level, splenic atrophy, and upregulated the expression of TNF-α, IL-6, and IL-1β, genes that are associated with skin inflammatory factors. In addition, Western blot results showed that PFNA treatment upregulated the expression of p-JNK protein. Additionally, cellular experiments indicated that RAW264.7 macrophages and mouse brain microvascular endothelial (bEnd.3) cells treated with PFNA at concentrations of 0.01–100 μM for 72 h showed no changes in cell viability. However, 100 μM PFNA upregulated the mRNA expression levels of the pro-inflammatory cytokines IL-1β and IL-6, as well as the protein expression of p-JNK, in RAW264.7 cells induced with 1 mg/mL LPS for 2 h. Similarly, PFNA increased TNF-α and IL-6 mRNA expression and p-JNK protein expression in bEnd.3 cells stimulated with 20 ng/mL TNF-α for 0.5 h. Based on these findings, we can conclude that PFNA may aggravate atopic dermatitis by promoting inflammation. Full article

Endothelial dysfunction appears early in type 1 diabetes (T1D). The detection of the first vascular disturbances in T1D patients is crucial, and the introduction of novel techniques, such as flow-mediated skin fluorescence (FMSF) and adaptive optics retinal camera (Rtx) imaging, gives hope for better detection and prevention of angiopathies in the future. In this study, we aimed to investigate microcirculation disturbances in pediatric patients with T1D with the use of FMSF and Rtx imaging. This research focused especially on the relationship between microvascular parameters obtained in FMSF and Rtx measurements, and the glycemic control evaluated in continuous glucose monitoring (CGM) reports. We observed significantly increased wall thickness (WT) and wall-to-lumen ratio (WLR) values in T1D patients in comparison to the control group. Although we did not observe significant differences between the T1D and control groups in the FMSF results, a trend toward significance between the time in range (TIR) and hyperemic response (HR_max) and an interesting correlation between the carotid intima-media thickness (cIMT_max) and HR_max. were observed. In conclusion, FMSF and Rtx measurments are innovative techniques enabling the detection of early microvascular disturbances. Full article

Background and Clinical Significance: Kaposi sarcoma (KS) is a rare angio-proliferative mesenchymal tumor that predominantly affects the skin and mucous membranes but may involve lymph nodes and visceral organs. Clinically, it manifests as red-purple-brown papules, nodules, or plaques, either painless or painful, often with disfiguring potential. The diagnosis is traditionally based on clinical and histopathological evaluation, although non-invasive imaging techniques are increasingly used to support diagnosis and treatment monitoring. We report a case of HHV-8-negative Kaposi sarcoma evaluated with multiple non-invasive imaging modalities to highlight their diagnostic utility. Case Presentation: An 83-year-old man presented with multiple painful, violaceous papulo-nodular lesions, some ulcerated, on the lateral aspect of his left foot. Dermoscopy revealed the characteristic rainbow pattern. Dynamic Optical Coherence Tomography (D-OCT) allowed real-time visualization of microvascular abnormalities, identifying large serpentine and branching vessels with clearly delineated capsules. Line-field Optical Coherence Tomography (LC-OCT) showed irregular dermal collagen, vascular lacunae, and the presence of spindle cells and slit-like vessels. Histological analysis confirmed the diagnosis of Kaposi sarcoma, revealing a proliferation of spindle-shaped endothelial cells forming angulated vascular spaces, with red blood cell extravasation and a mixed inflammatory infiltrate. Conclusions: Non-invasive imaging tools, including dermoscopy, D-OCT, and LC-OCT, have emerged as valuable adjuncts in the diagnosis and monitoring of KS. These techniques enable in vivo assessment of vascular architecture and tissue morphology, enhancing clinical decision-making while reducing the need for immediate biopsy. Dermoscopy reveals polychromatic vascular features, such as the rainbow pattern, while D-OCT and LC-OCT provide high-resolution insights into vascular proliferation, tissue heterogeneity, and cellular morphology. Dermoscopy, dynamic OCT, and LC-OCT represent promising non-invasive diagnostic tools for the assessment of Kaposi sarcoma. These technologies provide detailed morphological and vascular information, enabling earlier diagnosis and more personalized management. While histopathology remains the gold standard, non-invasive imaging offers a valuable complementary approach for diagnosis and follow-up, particularly in complex or atypical presentations. Ongoing research and technological refinement are essential to improve accessibility and clinical applicability. Full article

SARS-CoV-2, a β-coronavirus, primarily affects the lungs, with non-specific lesions and no cytopathic viral effect in the skin. Cutaneous antiviral mechanisms include activation of TLR/IRF pathways and production of type I IFN. We evaluated the antiviral mechanisms involved in the skin of COVID-19 patients, including skin samples from 35 deceased patients who had contracted COVID-19 before the launch of the vaccine. Detection of SARS-CoV-2 in the skin was performed using transmission electron microscopy and RT-qPCR. Microscopic and molecular effects of the virus in skin were evaluated by histopathology, RT-qPCR, and immunohistochemistry (IHC). The results revealed the presence of SARS-CoV-2 and microscopic changes, including microvascular hyaline thrombi, perivascular dermatitis, and eccrine gland necrosis. There was increased transcription of TBK1 and a reduction in transcription of TNFα by RT-qPCR in the COVID-19 group. IHC revealed reduced expression of ACE2, TLR7, and IL-6, and elevated expression of IFN-β by epidermal cells. In the dermis, there was decreased expression of STING, IFN-β, and TNF-α and increased expression of IL-6 in sweat glands. Our results highlight the role of type I IFN in the skin of COVID-19 patients, which may modulate the cutaneous response to SARS-CoV-2. Full article

ABCC6, a key regulator in ectopic calcification, plays a crucial role in mineralization through the modulation of extracellular purinergic pathways and production of inorganic pyrophosphate (PPi), which inhibits calcification. Inherited deficiencies in ABCC6 lead to pseudoxanthoma elasticum (PXE) and related conditions, characterized by calcification in various tissues, particularly affecting the skin, eyes, and cardiovascular system. Although PXE does not directly impact the nervous system, secondary neurological issues arise from cerebrovascular complications, increasing the risk of strokes linked to arterial blockages resembling atherosclerosis. This review investigates the connection between ABCC6 mutations and cerebral small vessel disease (SVD), expanding the understanding of PXE and related phenotypes. Mutations in ABCC6, identified as causing PXE, contribute to systemic metabolic dysfunction, with significant implications for cerebrovascular health. An association between ABCC6 mutations and cerebral SVD has been suggested in various studies, particularly in populations with distinct genetic backgrounds. Emerging evidence indicates that pathogenic mutations increase the risk of ischemic strokes, with both homozygous and heterozygous carriers showing susceptibility. Mechanistically, ABCC6 deficiency is implicated in dyslipidemia and atherosclerosis, further exacerbating cerebrovascular risks. Increased arterial pulsatility, linked to carotid siphon calcification, may also contribute to microvascular damage and subsequent brain injury. Understanding these mechanisms is vital for developing targeted diagnostic and therapeutic strategies for managing cerebrovascular risks in PXE patients. This review emphasizes the need for comprehensive genetic screening and the consideration of traditional vascular risk factors in patient management, highlighting the complex interplay between genetic mutations and environmental influences affecting cerebrovascular health. Future research should focus on longitudinal studies to elucidate the causal pathways linking arterial calcification, pulsatility, and brain damage in PXE. Full article

Background and Objectives: Penile tissue loss, which can be an acquired condition due to trauma or infection, but is also seen in congenital anomalies, is a rare condition in children. A standard surgical approach is often not possible due to the different degrees and etiologies of penile tissue loss. The continuing growth and the presence of various congenital anomalies in children require a different penile reconstruction approach than in adults. We aimed to share our experience and surgical results with children in whom we performed penile reconstruction with different techniques due to penile tissue loss. Materials and Methods: Ten cases that underwent penile reconstruction between 2018 and 2023 were evaluated retrospectively. Age at initial operation, associated anomalies, surgical technique, and other related surgical attempts, as well as functional and cosmetic results, were recorded. Results: Ten boys aged between 6 months and 17 years underwent phalloplasty due to penile tissue absence. In six cases, penile tissue loss was due to acquired causes, and in four cases, congenital anomalies were the reason. The most common cause of penile tissue loss was circumcision complications. In four cases, penile reconstruction was achieved by mobilization of the remaining corpus cavernosum tissues, in two cases, the cavernous tissue was adequate and repaired with glansplasty and penile skin graft. Phalloplasty was performed by tubularization of a skin and subcutaneous fat flap, removed from the pubic region and scrotal region, in two cases. A microvascular radial forearm flap was performed in a 17-year-old patient with penile tissue loss because of trauma, and a free skin flap taken from the forearm was used for penile reconstruction. Thirty percent of patients required a second surgery. Urinary continence was present in eight of the cases. Although four cases were classified as cosmetically unsatisfactory in our evaluation, all patients and their families reported being satisfied with the cosmetic results. Conclusions: Penile reconstruction for penile tissue loss in children should be performed in clinics where different scenarios can be applied. With maximum preservation and mobilization of existing cavernous tissues, temporary penile reconstruction with local flaps should be performed in young children at an early stage to minimize the psychological effects of penile absence. Although an esthetically perfect result cannot be guaranteed, patients and families are generally satisfied with the outcome. Full article

Introduction: The indication for a free flap in acute burn reconstruction is very specific. It should avoid several complications that are more common in the burned patient population. We propose an anterolateral thigh (ALT) flap as a first option for primary burn reconstruction in microvascular free flap reconstruction in burned patients. Patients and Methods: A retrospective review of all acutely burned patients treated with microvascular ALT free flap reconstruction between the years 2005 and 2022 in the Vall d’Hebron Barcelona Hospital Campus Burn Centre was conducted. Results: We performed 30 ALT flaps for primary burn reconstruction. The majority of patients were male (87.5%), with a mean age of 36.7 years, and 37% of patients were smokers. High-voltage electrical burns were the most common etiology. The mean time between burn injury and microsurgery was 22 days. The main recipient site was the lower limb. The flap survival rate was 96.6%. One patient required a meshed skin graft to cover a defect in the proximal third due to peripheral flap necrosis. One flap experienced mild congestion, which resolved spontaneously. Another flap had a local infection, which resolved with antibiotic therapy and surgical debridement. Conclusions: An ALT flap offers several advantages to a burned patient, provided that the surgical technique and postoperative management described in this study are followed. We propose it as the first option for primary burn reconstruction using free flaps in a burned patient. Full article

Microcirculatory oscillations known as flowmotion are a recognized feature of blood flow that reflect the functional state of the vascular system. Many diseases are associated with impaired flowmotion, especially diseases that are accompanied by hypoxia. Low-frequency myogenic oscillations (0.052–0.15 Hz) are an important regulator of microvascular adaptation to hypoxia. Here, we study the myogenic component of flowmotion using the FMSF–PORH (Flow Mediated Skin Fluorescence–Post Occlusive Reactive Hyperemia) technique. Myogenic oscillations were strongly activated under hypoxic conditions caused by occlusion of the brachial artery or intermittent hypoxic treatment. A strong correlation was noted between the hypoxia sensitivity parameter HS (the intensity of myogenic oscillations activated by hypoxia) and the normoxic myogenic flowmotion parameter VM (the intensity of myogenic oscillations under normoxic conditions). If HS is considered as a direct measure of the microcirculation response to hypoxia, then VM can be considered a measure of the microcirculation’s readiness to provide this response. The predictive value of the VM parameter is presented. The assessment of myogenic activity under normoxia conditions could thus provide a simple and rapid diagnostic tool for health care practitioners. Full article

3-O-Methyl-D-chiro-inositol (pinitol) has been reported to possess insulin-like effects and is known as one of the anti-diabetic agents for improving muscle and liver function. However, the beneficial effects of pinitol on human dermal microvascular endothelial cells (HDMECs) are not well understood. In this study, we investigated whether pinitol could protect HDMECs from damage induced by lipopolysaccharides (LPSs), which cause various cell defects. We observed that pinitol enhanced wound healing for LPS-damaged HDMECs. We found that pinitol significantly downregulated the LPS-induced upregulation of reactive oxygen species (ROS). Pinitol also significantly restored the mitochondrial membrane potential in these cells. Immunofluorescence analysis revealed that pinitol notably reduced the nuclear localization of NF-κB in LPS-damaged HDMECs. Furthermore, we demonstrated that pinitol decreased the phosphorylation levels of the MAPK family in LPS-damaged HDMECs. Interestingly, we observed that pinitol improved tube formation in LPS-damaged HDMECs. Taken together, we suggest that pinitol exerts several beneficial effects on LPS-damaged HDMECs and may be a promising therapeutic agent for improving vascular-related skin diseases. Full article

Background/Objectives: Patients with psoriasis exhibit endothelial dysfunction (EDy), which increases their cardiovascular risk. Excessive salt intake impairs endothelium-dependent vascular reactivity. However, research on EDy in psoriasis has focused primarily on larger vessels, leaving skin microcirculation unexplored. This study aimed to investigate the effects of a low-salt diet (LS diet, ~3.75 g/day) on microvascular reactivity in patients with chronic plaque psoriasis. Methods: Laser Doppler flowmetry was used to assess skin microcirculation blood flow in response to vascular occlusion (postocclusive reactive hyperemia, PORH), acetylcholine (acetylcholine-induced dilation, AChID), sodium nitroprusside (SNP-induced dilation, SNPID), and local heating (local thermal hyperemia, LTH). Blood and 24 h urine samples were collected for biochemical and inflammatory parameters and dietary adherence monitoring. Results: The results showed significant reductions in systolic (p = 0.021) and mean arterial blood pressure (p = 0.007) after the LS diet. AChID increased by 16% (p = 0.029) regardless of blood pressure changes, especially in normolipemic, normotensive patients without excess visceral fat. Importantly, significant sex differences were observed, with significant improvement in endothelial function observed only in women (p = 0.031 vs. p = 0.477). PORH did not change significantly; however, a Fourier transformation analysis revealed that the endothelial component of the PORH was significantly improved following the LS diet protocol. The duration of psoriasis negatively correlated with changes in AChID (R = −0.46, p = 0.036) and LTH (R = −0.45, p = 0.041) after the LS diet, indicating that prolonged low-grade inflammation reduced endothelial function reversibility. Additionally, lower triglyceride, uric acid, and BMI levels were significant predictors of better endothelial function improvement following the LS diet. Conclusions: This study supports the beneficial effect of the early introduction of an LS diet in the treatment protocols for patients with psoriasis. Full article

Background: Aminaphtone is a well-established pharmaceutical agent that has been utilized for over 40 years, primarily due to its effectiveness in treating microvascular disorders. Recent studies have explored its impact on various conditions, including chronic venous insufficiency, diabetic microangiopathy, leg ulcers, systemic sclerosis, and Raynaud’s phenomenon. These investigations have consistently demonstrated that aminaphtone enhances skin blood perfusion and mitigates endothelial damage, all while maintaining a robust safety profile over time. Case Summary: This report highlights the potential of aminaphtone in improving microcirculation in a young patient who experienced spontaneous capillary rupture in her second finger. A 38-year-old woman with undifferentiated connective tissue disease presented to the clinic for periungual videocapillaroscopy (NVC). Given the microangiopathic changes observed during the NVC, she was prescribed aminaphtone. After seven months of treatment, a follow-up NVC revealed significant improvement in the capillaroscopic findings. A comprehensive literature review on aminaphtone was conducted using electronic databases (PUBMED, Google Scholar, ResearchGate, UpToDate), along with manual searches, focusing on articles published until November 2024. Conclusion: Treatment with aminaphtone led to notable improvements in microangiopathic health. Following the introduction of this medication, the nailfold microvascular bed, which previously exhibited severe alterations, showed a remarkable transition to only mild abnormalities. Full article

Dermal substitutes require sufficient tissue integration and vascularization to be successfully covered with split-thickness skin grafts. To rapidly achieve this, we provide the proof of principle for a novel vascularization strategy with high translational potential. Nanofat was generated from subcutaneous adipose tissue of green fluorescence protein (GFP)⁺ C57BL/6J donor mice and seeded onto small samples (4 mm in diameter) of the clinically approved dermal substitute Integra^®. These samples and non-seeded controls were then implanted into full-thickness skin defects in the dorsal skinfold chamber of C57BL/6J wild-type mice and analyzed by intravital fluorescence microscopy, histology and immunohistochemistry over a 14-day period. Nanofat-seeded dermal substitutes exhibited an accelerated vascularization, as indicated by a significantly higher functional microvessel density on days 10 and 14 when compared to controls. This was primarily caused by the reassembly of GFP⁺ microvascular fragments inside the nanofat into microvascular networks. The improved vascularization promoted integration of the implants into the surrounding host tissue, which finally exhibited an increased formation of a collagen-rich granulation tissue. There were no marked differences in the inflammatory host tissue reaction to nanofat-seeded and control implants. These findings demonstrate that nanofat significantly improves the in vivo performance of dermal substitutes without affecting their biocompatibility. Full article

This review summarizes studies dedicated to the assessment of microvascular function based on microcirculatory oscillations monitored by the Flow-Mediated Skin Fluorescence (FMSF) technique. Two approaches are presented. The first approach uses oscillatory parameters measured under normoxic conditions, expressed as flowmotion (FM), vasomotion (VM), and the normoxia oscillatory index (NOI). These parameters have been used for the identification of impaired microcirculatory oscillations associated with intense physical exercise, post-COVID syndrome, psychological stress, and erectile dysfunction. The second approach involves characterization of the microcirculatory response to hypoxia based on the measurement of hypoxia sensitivity (HS). The HS parameter is used to characterize microvascular complications in diabetes, such as diabetic kidney disease and diabetic foot ulcers. Based on research conducted by the authors of this review, the FMSF parameter ranges characterizing microvascular function are presented. The diagnostic approach to assessing microvascular function based on flowmotion monitored by the FMSF technique has a wide range of applications and the potential to be integrated into widespread medical practice. Full article

Introduction: Nailfold video-capillaroscopy (NVC) is a non-invasive cost-effective technique involving the microscopic examination of small blood vessels of the distal nailfold with a magnification device. It provides valuable information regarding the microcirculation including anomalies such as tortuous or dilated capillaries, hemorrhages, and avascular areas, which can characterize connective tissue diseases. The utility of NVC in the diagnosis and monitoring of systemic sclerosis (SSc) has been investigated in numerous studies allowing the distinction of the specific microvascular pattern of scleroderma from different conditions other than scleroderma (non-scleroderma pattern). Sarcoidosis (SA) is a systemic inflammatory disease that can affect various organs, including the lungs, skin, and lymph nodes. The purpose of our review was to evaluate the current state of the art in the use of NVC in the diagnosis of SA, to understand the indications for its use and any consequent advantages in the management of the disease in different settings in terms of benefits for patients. Materials and Methods: We searched for the key terms “sarcoidosis” and “video-capillaroscopy” in a computerized search of Pub-Med, extending the search back in time without setting limits. We provided a critical overview of the literature, based on a precise evaluation. After our analysis, we examined the six yielded works looking for answers to our questions. Results: Few studies have evaluated that microcirculation is often compromised in SA, with alterations in blood flow and consequent tissue damage. Discussion: Basing on highlighted findings, NVC appears to be a useful tool in the initial evaluation of sarcoidosis patients. Furthermore, capillaroscopy is useful in the evaluation of the coexistence of sarcoidosis and scleroderma spectrum disorder or overlap syndromes. Conclusions: In conclusions, no specific pattern has been described for sarcoidosis, and further re-search is needed to fully understand the implications of nailfold capillaroscopy find-ings in this disease and to establish standardized guidelines for its use in clinical practice. Full article

Optical Coherence Tomography (OCT)-based angiography (OCTA) is a high-resolution, high-speed, and non-invasive imaging method that can provide vascular mapping of subcutaneous tissue up to approximately 2 mm. In dermatology applications of OCTA, handheld probes are always designed with a piece of transparent but solid contact window placed at the end of the probe to directly contact the skin for achieving better focusing between the light source and the tissue, reducing noise caused by minor movements. The pressure between the contact window and the skin is usually uncontrollable, and high external pressure affects the quality of microvascular imaging by compressing the vessels and obstructing the underlying blood flow. Therefore, it is necessary to determine a pressure range to ensure that the vessels can be fully imaged in high-quality images. In this paper, two pressure sensors were added to the existing handheld OCT probe, and the imaging probe was fixed to a metal stand and adjusted vertically to change the pressure between the probe and the tested skin site, a gradient of roughly 4 kPa (with 1–2 kPa error) increase was applied in each experiment, and the impact of pressure to the vessel was calculated. The experiment involved a total of five subjects, three areas of which were scanned (palm, back of the hand, and forearm). The vessel density was calculated to evaluate the impact of external pressure on angiography. In addition, PSNR was calculated to ensure that the quality of different tests was at a similar level. The angiography showed the highest density (about 10%) when the pressure between the contact window on the probe and the test area was between 3 and 5 kPa. As the pressure increased, the vascular density decreased, and the rate of decrease varied in different test areas. After fitting all the data points according to the different sites, the slope of the fitted line, i.e., the rate of decrease in density per unit value of pressure, was found to be 4.05% at the palm site, 6.93% at the back of the hand, and 4.55% at the forearm site. This experiment demonstrates that the pressure between the skin and contact window is a significant parameter that cannot be ignored. It is recommended that in future OCTA data collection processes and probe designs, the impact of pressure on the experiment be considered. Full article